• Archives of Pharmacal Research
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• 제29권5호
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• pp.384-393
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• 2006

Protein carboxylmethylation methylates the free carboxyl groups in various substrate proteins by protein carboxyl O-methyltransferase (PCMT) and is one of the post-translational modifications. There have been many studies on protein carboxylmethylation. However, the precise functional role in mammalian systems is unclear. In this study, immunoglobulin, a specific form of $\gamma-globulin$, which is a well-known substrate for PCMT, was chosen to investigate the regulatory roles of protein carboxylmethylation in the immune system. It was found that the anti-BSA antibody could be carboxylmethylated via spleen PCMT to a level similar to $\gamma-globulin$. This carboxylmethylation increased the hydrophobicity of the anti-BSA antibody up to 11.4%, and enhanced the antigen-binding activity of this antibody up to 24.6%. In particular, the Fc region showed a higher methyl accepting capacity with 80% of the whole structure level. According to the amino acid sequence alignment, indeed, 7 aspartic acids and 5 glutamic acids, as potential carboxylmethylation sites, were found to be conserved in the Fc portion in the human, mouse and rabbit. The carboxylmethylation of the anti-BSA antibody was reversibly demethylated under a higher pH and long incubation time. Therefore, these results suggest that protein carboxylmethylation may reversibly regulate the antibody-mediated immunological events via the Fc region.

• Nuclear Engineering and Technology
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• 제5권4호
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• pp.265-278
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• 1973

분자의 병진운동과 회전운동의 상관함수에 대한 감쇠함수 모델을 사용하여 분자액체의 비간섭중성자 산란단면적을 분석하였다. 이러한 방법은 직접적으로 산란함수를 구한다는 점에서 중간함수를 거치는 종래의 방법과는 판연히 다르다. 감쇠함수는 그장파장극한과 일반진동수 분포함수간의 간단한 관계에서 결정하였고 병진운동과회전 운동의 결합관계는 무시된다고 가정하였다. 분자질량중심의 병진운동은 그 짧은 시간과 장시간에서의 행위를 적절히 기술하는 물리적 모텔을 사용하였고 회전운동은 쌍극상관함수 또는 적외선진동 홈수스펙트럼의 푸리어 변환으로 된 감쇠함수에 관계된다고 가정하였다. 액체메탄에 대한 이론적 절대 산란강도를 계산하였으며 이는 열 및 냉중성자 측정치와 만족할만한 일치를 보여주고 있다.

• Molecules and Cells
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• 제43권2호
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• pp.168-175
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• 2020

Runx2 is an essential transcription factor for skeletal development. It is expressed in multipotent mesenchymal cells, osteoblast-lineage cells, and chondrocytes. Runx2 plays a major role in chondrocyte maturation, and Runx3 is partly involved. Runx2 regulates chondrocyte proliferation by directly regulating Ihh expression. It also determines whether chondrocytes become those that form transient cartilage or permanent cartilage, and functions in the pathogenesis of osteoarthritis. Runx2 is essential for osteoblast differentiation and is required for the proliferation of osteoprogenitors. Ihh is required for Runx2 expression in osteoprogenitors, and hedgehog signaling and Runx2 induce the differentiation of osteoprogenitors to preosteoblasts in endochondral bone. Runx2 induces Sp7 expression, and Runx2, Sp7, and canonical Wnt signaling are required for the differentiation of preosteoblasts to immature osteoblasts. It also induces the proliferation of osteoprogenitors by directly regulating the expression of Fgfr2 and Fgfr3. Furthermore, Runx2 induces the proliferation of mesenchymal cells and their commitment into osteoblast-lineage cells through the induction of hedgehog (Gli1, Ptch1, Ihh), Fgf (Fgfr2, Fgfr3), Wnt (Tcf7, Wnt10b), and Pthlh (Pth1r) signaling pathway gene expression in calvaria, and more than a half-dosage of Runx2 is required for their expression. This is a major cause of cleidocranial dysplasia, which is caused by heterozygous mutation of RUNX2. Cbfb, which is a co-transcription factor that forms a heterodimer with Runx2, enhances DNA binding of Runx2 and stabilizes Runx2 protein by inhibiting its ubiquitination. Thus, Runx2/Cbfb regulates the proliferation and differentiation of chondrocytes and osteoblast-lineage cells by activating multiple signaling pathways and via their reciprocal regulation.

• Journal of Animal Science and Technology
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• 제63권5호
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• pp.1142-1158
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• 2021

Short-chain fatty acids (SCFAs) are metabolic products produced during the microbial fermentation of non-digestible fibers and play an important role in metabolic homeostasis and overall gut health. In this study, we investigated the effects of supplementation with multispecies probiotics (MSPs) containing Bacillus amyloliquefaciens, Limosilactobacillus reuteri, and Levilactobacillus brevis on the gut microbiota, and fecal SCFAs and lactate levels of weaned pigs. A total of 38 pigs weaned at 4 weeks of age were fed either a basal diet or a diet supplemented with MSPs for 6 weeks. MSP administration significantly increased the fecal concentrations of lactate (2.3-fold; p < 0.01), acetate (1.8-fold; p < 0.05), and formate (1.4-fold; p < 0.05). Moreover, MSP supplementation altered the gut microbiota of the pigs by significantly increasing the population of potentially beneficial bacteria such as Olsenella, Catonella, Catenibacterium, Acidaminococcus, and Ruminococcaceae. MSP supplementation also decreased the abundance of pathogenic bacteria such as Escherichia and Chlamydia. The modulation of the gut microbiota was observed to be strongly correlated with the changes in fecal SCFAs and lactate levels. Furthermore, we found changes in the functional pathways present within the gut, which supports our findings that MSP modulates the gut microbiota and SCFAs levels in pigs. The results support the potential use of MSPs to improve the gut health of animals by modulating SCFAs production.

• Korean Chemical Engineering Research
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• 제57권1호
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• pp.85-89
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• 2019

무세포 단백질 합성 시스템은 세포를 파쇄한 후 파쇄액 내의 단백질 합성기구들을 이용하여 단백질을 발현하는 시스템으로 기존의 세포 기반 재조합 단백질 발현 기법들과 달리 세포의 생장조건에 영향을 받지 않으면서 발현 조절에 관한 다양한 인자들을 인위적으로 조절 할 수 있는 장점이 있다. 그러나, 단백질 합성 과정 중 소모되는 ATP의 연속적 재생을 위해 사용되는 에너지원의 높은 비용과 낮은 안정성은 재조합 단백질 대량생산에의 적용을 제약하는 요인으로 작용하여 왔다. 이러한 문제를 해결하기 위한 대안들 중의 하나로 포도당을 에너지원으로 사용하여 세포 파쇄액내 대사과정을 통해 ATP를 재생하는 방법이 있다. 본 연구에서는 포도당을 에너지원으로 이용한 무세포 합성 시스템에서의 단백질 합성 효율 향상을 위하여 대장균 파쇄액으로부터 회수된 지질을 추가적으로 첨가함으로써 산화적 인산화 과정에서의 ATP재생을 증진시키고자 하였다. 그 결과, 지질이 추가된 무세포 단백질 합성 시스템은 지질이 추가되지 않은 대조군에 비하여 6배 이상 향상된 단백질 생산성을 나타내었다.

• Translational and Clinical Pharmacology
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• 제26권3호
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• pp.128-133
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• 2018

Appropriate prescription writing is one of the critical medical processes affecting the quality of public health care. However, this is a complex task for newly qualified intern doctors because of its complex characteristics requiring sufficient knowledge of medications and principles of clinical pharmacology, skills of diagnosis and communication, and critical judgment. This study aims to gather data on the current status of undergraduate prescribing education in South Korea. Two surveys were administered in this study: survey A to 26 medical schools in South Korea to gather information on the status of undergraduate education in clinical pharmacology; and survey B to 244 intern doctors in large hospitals to gather their opinions regarding prescribing education and ability. In survey A, half of the responding institutions provided prescribing education via various formats of classes over two curriculums including lecture, applied practice, group discussions, computer-utilized training, and workshops. In survey B, we found that intern doctors have the least confidence when prescribing drugs for special patient populations, especially pregnant women. These intern doctors believed that a case-based practical training or group discussion class would be an effective approach to supplement their prescribing education concurrently or after the clerkship in medical schools or right before starting intern training with a core drug list. The results of the present study may help instructors in charge of prescribing education when communicating and cooperating with each other to improve undergraduate prescribing education and the quality of national medical care.

• Translational and Clinical Pharmacology
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• 제25권2호
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• pp.63-66
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• 2017

Allopurinol-induced severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome are reportedly associated with the $HLA-B^{\star}58:01$ genotype. Three patients who developed SCARs after allopurinol administration were subjected to HLA-B genotyping and lymphocyte activation test (LAT) to evaluate genetic risk and to detect the causative agent, respectively. All three patients given allopurinol to treat gout were diagnosed with DRESS syndrome. Symptom onset commenced 7-24 days after drug exposure; the patients took allopurinol (100-200 mg/d) for 2-30 days. HLA-B genotyping was performed using a polymerase chain reaction (PCR)-sequence-based typing (SBT) method. All patients had a single $HLA-B^{\star}58:01$ allele: $HLA-B^{\star}13:02/^{\star}58:01$ (a 63-year-old male), $HLA-B^{\star}48:01/^{\star}58:01$ (a 71-year-old female), and $HLA-B^{\star}44:03/^{\star}58:01$ (a 22-year-old male). Only the last patient yielded a positive LAT result, confirming that allopurinol was the causative agent. These findings suggest that patients with $HLA-B^{\star}58:01$ may develop SCARs upon allopurinol administration. Therefore, HLA-B genotyping could be helpful in preventing serious problems attributable to allopurinol treatment, although PCR-SBT HLA-B genotyping is time consuming. A simple genotyping test is required in practice. LAT may help to identify a causative agent.

• BMB Reports
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• 제54권2호
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• pp.142-147
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• 2021

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG phosphorothioate (PS CpG-ODN) are known to decrease IgE synthesis in Th2 allergy responses. Nonetheless, the therapeutic role of PS CpG-ODN is limited due to cytotoxicity. Therefore, we developed a phosphodiester (PO) form of CpG-ODN (46O) with reduced toxicity but effective against allergies. In this study, we first compared the toxicity of 46O with CpG-ODNs containing a PS backbone (1826S). We also investigated the therapeutic efficacy and mechanism of 46O injected intravenously in a mouse model of ovalbumin (OVA)-induced atopic dermatitis (AD). To elucidate the mechanism of 46O underlying the inhibition of IgE production, IgE- and TGF-β-associated molecules were evaluated in CD40/IL-4- or LPS/IL-4-stimulated B cells. Our data showed that the treatment with 46O was associated with a lower hematological toxicity compared with 1826S. In addition, injection with 46O reduced erythema, epidermal thickness, and suppressed IgE and IL-4 synthesis in mice with OVA-induced AD. Additionally, 46O induced TGF-β production in LPS/IL-4-stimulated B cells via inhibition of Smad7, which suppressed IgE synthesis via interaction between Id2 and E2A. These findings suggest that enhanced TGF-β signaling is an effective treatment for IgE-mediated allergic conditions, and 46O may be safe and effective for treating allergic diseases such as AD and asthma.

• 운동과학
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• 제26권2호
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• pp.103-114
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• 2017

INTRODUCTION: Regulation of skeletal muscle protein mass is implicated not only in exercise performance but in metabolic health. Exercise in combination with nutrition, particularly dietary protein/amino acid intake, are the pragmatic approach that effectively induces muscle anabolic response (i.e., muscle hypertrophy) through regulating protein synthesis and breakdown. PURPOSE: The purpose of this review was to summarize available data on the effect of exercise intervention and amino acids intake on muscle protein synthesis and breakdown and provide an insight into development of an effective exercise intervention and amino acids supplements, applicable to training practice. METHODS: In this review, we have reviewed currently available data mainly from stable isotope tracer studies with respect to the effect of exercise intervention and protein or amino acid supplement on muscle protein anabolic response. CONCLUSIONS: Taken together, exercise alone may not be effective in achieving a positive net muscle protein balance due to the fact that protein breakdown still exceeds protein synthesis until nutrition intake such as protein/amino acids. It appears that muscle anabolic response increases in proportional to the amount of protein intake up to 20 - 35 g depending on quality of protein, age, differences on exercise intensity, duration, and frequency, and individual's training status

• 한국콘텐츠학회논문지
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• 제21권5호
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• pp.422-434
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• 2021

본 연구는 아동의 가정과 학교에서 의견 청취 경험, 자아존중감, 그리고 인권 인식 간 구조적 관계를 탐색하는데 그 목적이 있다. 본 연구에서는 연구가설을 검증하기 위해 2017년 아동·청소년 인권실태 조사의 중·고등학생 응답(6,405명, 여자 47.8%)을 대상으로 Mplus를 사용하여 구조방정식 모형을 분석하였다. 그 결과는 다음과 같다. 첫째, 가정 또는 학교에서 의견이 청취된 경험을 한 아동일수록 자아존중감과 인권 인식이 높은 것으로 나타났다. 또한 자아존중감과 인권 인식은 정적인 관계를 보였으며, 자아존중감은 가정과 학교 각각에서의 의견이 청취된 경험이 인권 인식으로 이어지는 경로를 유의미하게 매개하였다. 추가적으로 인권교육을 받았는지의 유무에 따라 각 경로에 차이가 있는지 살펴본 결과 유의미한 차이는 없었다. 이러한 연구 결과를 토대로 아동의 인권 인식 증진을 위해 가정이나 학교에서 아동의 의견이 청취되는 환경조성을 위한 실천적 방안을 논의하였다.